Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibronectin is one of the cell adhesion proteins. Adhesion molecules play an important role in neural and synaptic genesis, and their dysfunction may result in neurodevelopmental abnormalities, which have been assumed to be a factor in the pathogenesis of schizophrenia. To examine the possible involvement of fibronectin in the etiology of schizophrenia, we analyzed six polymorphisms, located in introns 2, 21, 24, and 26, and exons 20 and 28, in the human fibronectin gene (FN1) of schizophrenic patients in the Japanese population (n = 104) and age-and gender-matched controls (n = 104). No significant positive association was observed between either of the polymorphisms and schizophrenia, nor was an association found between either of the polymorphisms and any subtypes of schizophrenia. These data did not provide evidence for a contribution of the FN1 gene to susceptibility to schizophrenia.
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PMID:Association study between the fibronectin gene and schizophrenia. 1249 12

Schizophrenia has been proposed to have a neurodevelopmental aetiology. Neural Cell Adhesion Molecule 1 (NCAM1) is involved in several neurodevelopmental processes and abnormal expression of this gene has been associated in the pathology of schizophrenia and, thus, altered NCAM1 expression may be characteristic of the early stages of the illness. Alternative splicing of the NCAM1 transcript produces 3 major isoforms. Using qPCR we analysed mRNA expression of one of these isoforms; the 180 kDa isoform of NCAM1 (NCAM-180), in Brodmann Area (BA) 46, BA10 and BA17, post-mortem, from 15 subjects with a short duration of illness of schizophrenia (<7 years) and 15 control subjects. NCAM-180 mRNA expression was increased in BA46 from subjects with schizophrenia compared to controls (p=0.013). By contrast, there were no significant differences in the expression of NCAM-180 mRNA in BA10 (p=0.575) or BA17 (p=0.772). We then analysed NCAM-180 mRNA expression in BA46 from 15 subjects with a longer duration of illness of schizophrenia (>22 years) and 15 controls. There was no significant difference in NCAM-180 mRNA expression in this second cohort. This data suggests NCAM-180 mRNA expression is altered in a regionally-specific manner in schizophrenia and these changes are associated with the early period following diagnosis.
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PMID:Regional and duration of illness differences in the alteration of NCAM-180 mRNA expression within the cortex of subjects with schizophrenia. 1941 Nov 61

Genetic and biomarker studies in patients have identified the Neural Cell Adhesion Molecule (NCAM) and its associated polysialic acid (PSA) as a susceptibility factors for schizophrenia. NCAM and polysialtransferase mutant mice have been generated that may serve as animal models for this disorder and allow to investigate underlying neurodevelopmental alterations. Indeed, various schizophrenia-relevant morphological, cognitive and emotional deficits have been observed in these mutants. Here we studied social interaction and attention of NCAM null mutant (NCAM(-/-)) mice as further hallmarks of schizophrenia. Nest building, which is generally associated with social behavior in rodents, was severely impaired, as NCAM(-/-) mice continuously collected smaller amounts of nest building material than their wild type littermates and built nests of poorer quality. However, social approach tested in a three-compartment-box was not affected and latent inhibition of Pavlovian fear memory was not disturbed in NCAM(-/-) mice. Although NCAM deficient mice do not display a typical schizophrenia-like phenotype, they may be useful for studying specific endophenotypes with relevance to the disease.
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PMID:Are NCAM deficient mice an animal model for schizophrenia? 2282 93

Schizophrenia (SZ) and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders that may share an underlying pathology suggested by shared genetic risk variants. We sequenced the exonic regions of 215 genes in 147 ASD cases, 273 SZ cases and 287 controls, to identify rare risk mutations. Genes were primarily selected for their function in the synapse and were categorized as: (1) Neurexin and Neuroligin Interacting Proteins, (2) Post-synaptic Glutamate Receptor Complexes, (3) Neural Cell Adhesion Molecules, (4) DISC1 and Interactors and (5) Functional and Positional Candidates. Thirty-one novel loss-of-function (LoF) variants that are predicted to severely disrupt protein-coding sequence were detected among 2 861 rare variants. We found an excess of LoF variants in the combined cases compared with controls (P=0.02). This effect was stronger when analysis was limited to singleton LoF variants (P=0.0007) and the excess was present in both SZ (P=0.002) and ASD (P=0.001). As an individual gene category, Neurexin and Neuroligin Interacting Proteins carried an excess of LoF variants in cases compared with controls (P=0.05). A de novo nonsense variant in GRIN2B was identified in an ASD case adding to the growing evidence that this is an important risk gene for the disorder. These data support synapse formation and maintenance as key molecular mechanisms for SZ and ASD.
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PMID:Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders. 2412 26

Developmental synaptic remodeling is important for the formation of precise neural circuitry, and its disruption has been linked to neurodevelopmental disorders such as autism and schizophrenia. Microglia prune synapses, but integration of this synapse pruning with overlapping and concurrent neurodevelopmental processes, remains elusive. Adhesion G protein-coupled receptor ADGRG1/GPR56 controls multiple aspects of brain development in a cell type-specific manner: In neural progenitor cells, GPR56 regulates cortical lamination, whereas in oligodendrocyte progenitor cells, GPR56 controls developmental myelination and myelin repair. Here, we show that microglial GPR56 maintains appropriate synaptic numbers in several brain regions in a time- and circuit-dependent fashion. Phosphatidylserine (PS) on presynaptic elements binds GPR56 in a domain-specific manner, and microglia-specific deletion of Gpr56 leads to increased synapses as a result of reduced microglial engulfment of PS+ presynaptic inputs. Remarkably, a particular alternatively spliced isoform of GPR56 is selectively required for microglia-mediated synaptic pruning. Our present data provide a ligand- and isoform-specific mechanism underlying microglial GPR56-mediated synapse pruning in the context of complex neurodevelopmental processes.
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PMID:A splicing isoform of GPR56 mediates microglial synaptic refinement via phosphatidylserine binding. 3245 62